The proposal is designed to address several unresolved questions related to the secretion of digestive enzymes by the acinar cells of the pancreas. We wish to perform studies which will enable us to describe: (1) the mechanisms by which carboxypeptidase A and carboxypeptidase B are formed from their respective zymogen precursors, procarboxypeptidase A and procarboxypeptidase B; (2) the structural and functional relationship of protease E, an elastase-related enzyme, and its zymogen, to the known enzymes of the chymotrypsin family; (3) the specificity of the protease which is responsible for processing pretrypsinogen in the rough endoplasmic reticulum of the acinar cell; and (4) the orientation of an Mr approximately-66,000 glycoprotein present in the limiting membranes of zymogen granules and its cellular-distribution following exocytosis. These questions would be investigated by the methods of protein chemistry, physical biochemistry, enzymology, and cell biology.